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PHYSIOLOGY OF MENSTRUATION
The female has a fixed number of gamets for
her reproductive life.
7 million oogonia at 20 weeks gestatation
700 000 at the time of birth
400 000 by puberty
100 000 by 30 35 years of age
PHYSIOLOGY OF MENSTRUATION
AND MENOPAUSE
Relative changes in FSH
as a Function of Life Stages
Life Stages
Chidhood
FSH (mIU/mL)
<4
Reproductive years
6 10
Perimenopause
14 24
Menopause
> 30
PHYSIOLOGY OF MENSTRUATION
AND MENOPAUSE
PERIMENOPAUSE
The period of 5 to 10 years before the menopause.
Symptoms:
Increasingly inefficient reproductive functions
PHYSIOLOGY OF MENSTRUATION
AND MENOPAUSE
Steroid Hormone Serum Concentrations
Premenopausal
Women
Postmenopausal
Women
Postoophorectomy
Testosterone
(ng/dl)
325
(200 600)
230
110
Androstendione
(ng/dl)
1500
(500 - 3000)
800 900
800 900
Estrone
(pg/ml)
30 200
25 30
30
Estradiol
(pg/ml)
35 - 500
10 - 15
15 - 20
Hormone
MENOPAUSE
The permanent cessation of menses
The mean age of women at menopause is 51
years
Approximately 4% of women undergo a
natural menopause befor 40 year of age
premature ovarian failure.
MENOPAUSE
Menopause is a physiologic process,
however, the consequences of ovarian
failure can diminish a womans quality of
life and can predispose her to osteoporosis
and increased risk of cardiovascular
disease.
PHYSIOLOGY OF MENSTRUATION
AND MENOPAUSE
PHYSIOLOGY OF MENSTRUATION
AND MENOPAUSE
The major source of postmenopausal
estrogens is adrenal androgens,
particulary androstendione, which
undergoes aromatization by
peripherial tissues to estrone.
MENOPAUSE
1.
2.
CATEGORIES OF SYMPTOMS:
Vasomotor disturbances:
hot flushes, night sweats, palpitations headaches,
muscle aches
Organ atrophy:
- vaginal dryness, atrophy, dyspareunia
- urinary incontinence, dysuria, infections
- brest atrophy
- skin dryness and thinning, brittle nails
MENOPAUSE
3.
4.
5.
CATEGORIES OF SYMPTOMS:
Changes in mood and libido:
anxiety, insomnia, depression, irritability,
inability to concentrate, lack of energy
Accelerated bone mineral loss leading to
osteoporosis (long term)
Coronary artery disease (long term)
HORMONAL REPLACEMENT
THERAPY
The indication for HRT:
HORMONAL REPLACEMENT
THERAPY
Types
of oestrogens
NATURAL
17-oestradiol
Oestradiol valerate
Oestrone piperazine
sulphat
Conjugated equine
oestrogens
Oestriol
SYNTHETIC
Ethinyloestradiol
Mestranol
Diethylstilboestrol
Dienoestrol
HORMONAL REPLACEMENT
THERAPY
Routes of estrogens administration
Oral
Transdermal
Intranasal
Transbucal
Transvaginal
Intravenous
Intramuscular
HORMONAL REPLACEMENT
THERAPY
Estrogens administration modes
Pulsatile administartion
HORMONAL REPLACEMENT
THERAPY
Mechanism of estrogen action
HORMONAL REPLACEMENT
THERAPY
Estro
gens estrogens produce fewer metabolic
The natural
side effects than synthetic
Synthetic estrogens with a steroid structure (i.e.
ethinyl estradiol) are most frequenty used in
oral contarception
Conjugated equine estrogens in use mostly in USA
Native human estrogens (i.e. 17-estradiol) or
estradiol valerate mostly in use in Europe
Estrogen supplementation
Oral
TTS
Arterial resistance
Uterine artery
Carotid artery
Oral TTS
0/
Ch-LDL
Triglyceride
Renine substrates
Blood preassure
Prostacycline
Estrogene supplementation
Oral
TTS
0/
0/
0/
0/
0/
0/
ESTROGEN INFLUENCE ON
CARBOHYDRATE METABOLISM
Transdermal E2 administration decreases the basal
insulin level and increases insulin clearanse, when
administrated orally does not influence insulin turnover
E2 decreases insulin resistance, conjugated E interacts
equivocally
E2 is necessary, among others, to support pancreatic
insulin secretion
ESTROGEN REPLACEMENT
BENEFITS IN BONES
Estrogen therapy given for at least 5
years early in the climacteric period
reduces subsequent hip and Colles
fracture by 50% and vertebral fractures
by up to 90%.
Consensus Development Conference, Copenhagen, 1990
GENETIC:
European or Asian race
Slender build
Previous osteoporotic fracture
Family history of osteoporosis
ENVIRONMENTAL:
Low exposure to sunlight
LIFESTYLE:
Low dietary calcium intake
Smoking
Chronic alcohol consumption
Sedentary lifestyle
HORMONAL FACTORS:
Early menopause
Nulliparity
OTHER DISEASES:
Liver disorders
Thyrotoxicosis
Hyperparathyroidism
Chronic debilitating illness
Prolonged immobility
Oral corticosteroid therapy
Postgastrectomy malabsorption states
HORMONAL REPLACEMENT
THERAPY
Types
of progestogens
19-Nortestosterone
Derivatives
Norethisteron acetate
Norethisteron
Levonorgestrel
Desogestrel
Gestodene
Lynestrol
Ethynodiol diacetate
Norgestimat
17-Hydroxyprogesterone
Derivatives
Medroxyprogesterone
acetate
Dydrogesterone
Megestrol acetate
Cyptoterone acetate
Medrogestone
HORMONAL REPLACEMENT
THERAPY
Progestogens
Progestogenic
effect
Androgenic
effect
Estrogenic
effect
Antiestrogenic
effect
Progesteron
Dydrogesteron
Medroxyprogest
eron acetate
++
Cyproterone
acetate
++
Norethinodron
++
++
Levonorgestrel
+++
+++
++
Norgestimate
+++
++
Desogestrel
+++
++
Gestodene
+++
++
++
HORMONAL REPLACEMENT
THERAPY
Progestogens
HORMONAL REPLACEMENT
THERAPY
Adverse effects of HRT
(thromboembolism, coronary artery disease,
brest and endometrial cancer)
are higly related to the drugs, dosage, regimen or
route of administration used, and to duration
of use
CONTRAINDICATIONS TO HRT
Pregnancy
Lactation
Severe disturbances of liver functions
Jaundice or persistent itching during previous
pregnancy
Previous or existing liver tumours
Estrogendepended tumors of uterus, ovaries or brest
or suspicion of such tumours
CONTRAINDICATIONS TO HRT
Endometriosis
Existing or previous thromboembolic
processes
Severe diabetes mellitus with vascular
changes
Sickle-cell anaemia
Disturbances of lipo-metabolism
CONTRAINDICATIONS TO HRT